chr3-175295775-C-A

Variant names:

• chr3-175295775-C-A
• rs4894708
• NM_207015.3:c.940-28400C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207015.3(NAALADL2):​c.940-28400C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 150,630 control chromosomes in the GnomAD database, including 16,696 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16696 hom., cov: 28)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 2 publications found

Genes affected

NAALADL2 (HGNC:23219): (N-acetylated alpha-linked acidic dipeptidase like 2) Predicted to enable metalloexopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within response to bacterium. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.940-28400C>A		intron_variant	Intron 4 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.940-28400C>A		intron_variant	Intron 4 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000414826.1	n.120+39245C>A		intron_variant	Intron 1 of 6	1		ENSP00000396969.1
NAALADL2	ENST00000473253.5	n.1172-28400C>A		intron_variant	Intron 4 of 10	2
NAALADL2	ENST00000489299.5	n.679-28400C>A		intron_variant	Intron 4 of 10	2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69211 AN: 150508 Hom.: 16681 Cov.: 28

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.460 AC: 69249 AN: 150630 Hom.: 16696 Cov.: 28 AF XY: 0.462 AC XY: 33919 AN XY: 73454

African (AFR) AF: 0.324 AC: 13325 AN: 41098

American (AMR) AF: 0.448 AC: 6762 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1605 AN: 3450

East Asian (EAS) AF: 0.413 AC: 2107 AN: 5106

South Asian (SAS) AF: 0.505 AC: 2394 AN: 4736

European-Finnish (FIN) AF: 0.593 AC: 6079 AN: 10254

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.526 AC: 35555 AN: 67588

Other (OTH) AF: 0.449 AC: 942 AN: 2098

Alfa AF: 0.477 Hom.: 3357

Bravo AF: 0.446

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.42
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4894708; hg19: chr3-175013564;